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Scientific article
Open access
English

Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence

Published inCell Host & Microbe, vol. 20, no. 3, p. 318-328
Publication date2016
Abstract

Some strains of the protozoan parasite Leishmania guyanensis (L.g) harbor a viral endosymbiont called Leishmania RNA virus 1 (LRV1). LRV1 recognition by TLR-3 increases parasite burden and lesion swelling in vivo. However, the mechanisms by which anti-viral innate immune responses affect parasitic infection are largely unknown. Upon investigating the mammalian host's response to LRV1, we found that miR-155 was singularly and strongly upregulated in macrophages infected with LRV1+ L.g when compared to LRV1- L.g. LRV1-driven miR-155 expression was dependent on TLR-3/TRIF signaling. Furthermore, LRV1-induced TLR-3 activation promoted parasite persistence by enhancing macrophage survival through Akt activation in a manner partially dependent on miR-155. Pharmacological inhibition of Akt resulted in a decrease in LRV1-mediated macrophage survival and consequently decreased parasite persistence. Consistent with these data, miR-155-deficient mice showed a drastic decrease in LRV1-induced disease severity, and lesional macrophages from these mice displayed reduced levels of Akt phosphorylation.

Keywords
  • Animals
  • Cell Survival
  • Disease Models, Animal
  • Immunity, Innate
  • Leishmania guyanensis/pathogenicity/physiology/virology
  • Leishmaniasis, Mucocutaneous/parasitology/pathology
  • Leishmaniavirus/immunology
  • Macrophages/immunology/parasitology
  • Mice
  • Mice, Knockout
  • MicroRNAs/metabolism
  • Proto-Oncogene Proteins c-akt/metabolism
  • Toll-Like Receptor 3/metabolism
Citation (ISO format)
EREN, Remzi Onur et al. Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence. In: Cell Host & Microbe, 2016, vol. 20, n° 3, p. 318–328. doi: 10.1016/j.chom.2016.08.001
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Article (Accepted version)
accessLevelPublic
Identifiers
ISSN of the journal1931-3128
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166downloads

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